CompDP: A Framework for Simultaneous Subgraph Counting Under Connectivity Constraints

The subgraph counting problem computes the number of subgraphs of a given graph that satisfy some constraints. Among various constraints imposed on a graph, those regarding the connectivity of vertices, such as "these two vertices must be connected," have great importance since they are indispensable for determining various graph substructures, e.g., paths, Steiner trees, and rooted spanning forests. In this view, the subgraph counting problem under connectivity constraints is also important because counting such substructures often corresponds to measuring the importance of a vertex in network infrastructures. However, we must solve the subgraph counting problems multiple times to compute such an importance measure for every vertex. Conventionally, they are solved separately by constructing decision diagrams such as BDD and ZDD for each problem. However, even solving a single subgraph counting is a computationally hard task, preventing us from solving it multiple times in a reasonable time. In this paper, we propose a dynamic programming framework that simultaneously counts subgraphs for every vertex by focusing on similar connectivity constraints. Experimental results show that the proposed method solved multiple subgraph counting problems about 10-20 times faster than the existing approach for many problem settings

Control of STING Agonistic/Antagonistic Activity Using Amine-Skeleton-Based c-di-GMP Analogues

Stimulator of Interferon Genes (STING) is a type of endoplasmic reticulum (ER)-membrane receptor. STING is activated by a ligand binding, which leads to an enhancement of the immune-system response. Therefore, a STING ligand can be used to regulate the immune system in therapeutic strategies. However, the natural (or native) STING ligand, cyclic-di-nucleotide (CDN), is unsuitable for pharmaceutical use because of its susceptibility to degradation by enzymes and its low cell-membrane permeability. In this study, we designed and synthesized CDN derivatives by replacing the sugar-phosphodiester moiety, which is responsible for various problems of natural CDNs, with an amine skeleton. As a result, we identified novel STING ligands that activate or inhibit STING. The cyclic ligand 7, with a cyclic amine structure containing two guanines, was found to have agonistic activity, whereas the linear ligand 12 showed antagonistic activity. In addition, these synthetic ligands were more chemically stable than the natural ligands

Effect of albumin on the absorption of phenol red, bromphenol blue and bromosulphonphthalein as model drugs from the liver surface membrane in rats,

The effect of bovine serum albumin (BSA) on drug absorption from the liver surface in rats was examined by using three organic anions (phenol red, bromphenol blue and bromosulphonphthalein) as model drugs which have a high affinity for albumin. The binding ratio of the model drugs (3 mg/ml in phosphate buffer) to BSA varied widely at a BSA concentration of 0.1--10% (w/v). The model drugs (3 mg/ml x 0.1 ml) with or without BSA were applied to the rat liver surface in vivo employing a cylindrical glass cell (i.d. 9 mm, area 0.64 cm2). The absorption ratios of the model drugs from the rat liver surface at 6h, calculated from the amount recovered from the glass cell, decreased with an increase in BSA concentration. A similar trend was observed with biliary recovery of the model drugs. A marked reduction in the absorption ratio was seen with bromosulphonphthalein, which has the highest binding activity to BSA among the three organic anions. Accordingly, protein binding appears to be a significant factor with respect to the drug absorption from the liver surface.グラフなしwithout graph

Absorption of phenol red and bromphenol blue as model drugs from the peritoneal cavity around the liver surface in rats

The effect of the injection site on the pharmacokinetics of phenol red and bromphenol blue as model drugs after intraperitoneal (i.p.) administration into rats was examined. Their absorption rate from the peritoneal cavity was faster after i.p. administration to the liver surface (LS) than that after i.p. administration to the distal small intestine (SI), as shown by the increase in maximum concentration and decrease in mean residence time in plasma. A similar tendency was observed in the biliary excretion pattern. The enhanced absorption rate was supported by the significantly smaller amount of both drugs remaining in the peritoneal cavity at 15 min after LS administration than that after SI administration. The liver concentration of the model drugs at 15 min after LS administration was 1.5 - 2.0 times higher than that after SI administration. Accordingly, LS administration was shown to be effective with good absorbability and efficient drug delivery to the liver.without figuresグラフな

Absorption of organic anions as model drugs following application to rat liver surface in-vivo

Absorption of organic anions (phenol red, bromphenol blue and bromosulphonphthalein) has been studied after their application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0.64 cm2). Every drug appeared gradually in the blood with the peak level at about 1 h, after which its concentration declined slowly. Absorbed model drug was efficiently excreted into the bile. These observations appear to indicate the possibility of drug absorption from liver surface membrane. Absorption ratios of model drugs were estimated to be more than 59 % in 6 h. As to phenol red, its biliary recovery and metabolism ratio did not change as compared with that of i.v. administration.without figuresグラフな

Effect of application volume and area on the absorption of phenol red as a model drug from the liver surface in rats

We examined the importance of application volume and area in the absorption of phenol red as a model drug from the rat liver surface, for pharmaceutical formulation concerning administration form. When 1 mg of phenol red was applied to the rat liver surface in-vivo using a cylindrical glass cell (i.d. 9 mm) in three volumes (0.1, 0.2 or 0.334 mL), the shape of the plasma concentration pattern differed greatly, particularly the maximum concentration. These patterns were well fitted by a two-compartment model with first-order absorption, and the obtained absorption rate constant Ka decreased inversely according to the application volume. The absorption ratio and biliary recovery of phenol red at 6 h was increased with glass cell area (i.d. 6, 9 or 14 mm; area 0.28, 0.64 or 1.54 cm2). Furthermore, the permeability coefficient Papp derived from Ka did not depend on application area, indicating no difference in absorption characteristics of liver surface. This also implies transport of a drug by a passive diffusion from the liver surface. After intraperitoneal administration to the rat liver surface for clinical application, increase in application volume resulted in the delayed disappearance of phenol red from plasma. However, the difference was not as marked as that using a glass cell. The assumption that the effective area relating to the absorption changed with the application volume enabled us to estimate Papp. Consequently, we speculate absorbability can be estimated precisely by considering application volume and area

Programs for calculating the statistical powers of detecting susceptibility genes in case–control studies based on multistage designs

Motivation: A two-stage association study is the most commonly used method among multistage designs to efficiently identify disease susceptibility genes. Recently, some SNP studies have utilized more than two stages to detect disease genes. However, there are few available programs for calculating statistical powers and positive predictive values (PPVs) of arbitrary n-stage designs